Clinical trials need to shift focus of treatments, says B.C. researcher

"Negative trials can be as meaningful as positive trials, (though) obviously it's a little bit more fun to do positive trials." - Dr. Edward Mills.

Vancouver Sun 4 minute read January 3, 2022

COVID-19’s Omicron variant has changed things considerably for researchers like Dr. Edward Mills.

He has been coordinating clinical trials of potential COVID treatments from his office near Granville Island.

“Omicron is a relatively mild disease for most people,” Mills said. “We now need to change our clinical trials to respond to that.”

Instead of searching out the treatments that are likely effective in reducing hospitalizations and death from COVID, Mills said researchers need to shift their benchmarks to include speeding up recovery from a less-virulent disease that will get patients back to work sooner.

“It’s quite a complicated issue and it’s quite … an unexpected spanner in the works for people doing trials,” said Mills, a McMaster University professor and co-principal investigator in the privately financed TOGETHER COVID trials initiative.

To date, it has been a race to scour the properties of known drugs and test those that might be helpful against COVID. The nine drugs that Mills’ group has put through clinical trials out of his Vancouver office have led to some important discoveries.

His team were the ones to identify the cheap antidepressant fluvoxamine as a potential early treatment to prevent hospitalization of at-risk COVID patients.

They were also among the first to show that hydroxychloroquine and the anti-parasite drug ivermectin are not effective treatments.

“We did hydroxychloroquine in the beginning and that was a very important trial because we showed that it didn’t work, even though there were people prescribing it,” Mills said.

Based on the strength of their results, other investigators stopped recruiting subjects for subsequent studies, he added.

“So negative trials can be as meaningful as positive trials, (although) obviously it’s a little bit more fun to do positive trials.”

Researchers have trialed everything from HIV treatments to diabetes drugs for potential repurposing, Mills said. Some, such as ivermectin, have wound up becoming political beyond the science that brought them up for consideration.

“In the beginning, there was a lot of scientific interest in (ivermectin),” Mills said, because in computer modelling, it showed “signals” the anti-parasite drug could be effective against the COVID virus.

The drug, however, “also indicates it works for Ebola and Zika (virus) and everything,” he added.

Mills’ group, however, conducted the largest trial to show that ivermectin is not an effective treatment for COVID alone.

Unfortunately, those promoting ivermectin as a treatment are doing so blindly, Mills said, while critics dismiss the treatment unscientifically as a “horse dewormer,” when it has plenty of uses in humans.

“It’s a fantastic drug for conditions like river blindness and parasitic infections,” Mills said.

And the reason he doesn’t believe ivermectin should be completely dismissed is because “we don’t understand the role of parasite co-infection during COVID,” Mills said, including places where there are a lot of parasitic infections that end up in the lungs of patients.

“If you’re genuinely treating those (parasite) infections, you probably are having an effect on the COVID outcomes,” Mills said.

The TOGETHER COVID initiative joins other Vancouver-based firms, such as Acuitas Therapeutics, which contributed to development of mRNA vaccines, and antibody-drug developer AbCellera playing key roles in dealing with COVID.

Mills, who is also an adjunct faculty member at Simon Fraser University, is conducting the trials with co-principal Dr. Gilmar Reis with the Universidade Catolica de Minas Gerais in Brazil, where they have been able to consistently recruit the number of patients they need.

They are also doing work through a private, not-for-profit company, backed by grants from foundations, Mills said, because they need to move faster than the pace that is typically allowed under university administration.

“At Granville Island, we do the planning, we obtain the funding, we design the study and monitor the study,” Mills said. “And we analyze the study and write it up.”

As for fluvoxamine, TOGETHER COVID found that 30 per cent of patients in a placebo-controlled study avoided hospitalization after treatment, versus 10 per cent in the placebo group, indicating its effectiveness.

And Ontario has added fluvoxamine to its guidelines as a treatment for use, along with Johns Hopkins and Harvard universities.

Their next step is to trial fluvoxamine in combination with an inhaled steroid as well as with the antiviral drug molnupiravir. And the medical journal Nature Medicine listed TOGETHER COVID one of “11 clinical trials that will shape medicine in 2022.”

“We’ve engaged about 20,000 patients around the world, we’ve randomized more than 4,000 (patients),” Mills said. “We’ve evaluated 11 different drugs and we’re changing guidelines around the world.”

What comes next with COVID is difficult to predict.

“I don’t have a magic 8-Ball,” Mills said, but the emergence of the Omicron variant, which hasn’t been as virulent of the previously dominant Delta variant offers a bit of optimism that COVID-19 might be on the way to becoming endemic, rather than a pandemic.

“(That means) everybody has some level of immunity to it, and that’s been observed in South Africa,” Mills said.